Background:Tumor recurrence severely impacts the prognosis of hepatocellular carcinoma(HCC)patients undergoing liver transplantation(LT).We aimed to explore novel and robust biomarkers for precise prediction of tumor ...Background:Tumor recurrence severely impacts the prognosis of hepatocellular carcinoma(HCC)patients undergoing liver transplantation(LT).We aimed to explore novel and robust biomarkers for precise prediction of tumor recurrence and prognosis following LT.Methods:Cancerous tissues of 252 HCC patients who underwent LT across three centers were included in the study.Tissue microarrays and in situ hybridization were utilized to assess the circ0006646 level.Kaplan-Meier method along with the log-rank test was performed to analyze overall survival and recurrence-free survival.To identify prognostic factors,particularly related to tumor recurrence,we conducted univariate and multivariate Cox regression analyses.Nomogram was constructed to predict the risk of tumor recurrence after LT and subsequently the efficacy of the nomogram was validated.Results:Elevated circ0006646 levels in HCC were associated with reduced survival and increased recurrence rates following LT(5-year overall survival:29.2%vs.60.4%,P<0.01;5-year recurrence-free survival:42.3%vs.63.0%,P<0.001).High circ0006646 expression was significantly correlated with higher Child-Pugh grade(P=0.040),larger total tumor diameter(P=0.033),and beyond the Milan criteria(P=0.033).Cox regression analysis unveiled that circ0006646 expression score,preoperative transarterial chemoembolization(TACE),positive HBsAg status,poor tumor differentiation and beyond the Hangzhou criteria were independent risk factors for post-transplant tumor recurrence,leading to the development of a novel nomogram for precise prediction.The nomogram demonstrated a reasonable prognostic effectiveness(area under the receiver operating characteristic curve=0.7636,C-index=0.745)and outperformed conventional models like the Milan criteria.Besides,the inclusion of circ0006646 enhanced the precision of the Milan and Hangzhou criteria.Moreover,circ0006646 served as a potent biomarker in alpha-fetoprotein(AFP)-negative HCC undergoing LT.Conclusions:circ0006646 is a novel and robust prognostic biomarker for predicting post-transplant survival and tumor recurrence in HCC patients.A nomogram integrating circ0006646 stands as a valuable prognostic instrument in LT for HCC.展开更多
BACKGROUND Hesperetin,a flavonoid predominantly present in citrus fruits,exhibits significant intervention effects on both the initiation and progression of gastric cancer.However,the specific mechanisms underlying th...BACKGROUND Hesperetin,a flavonoid predominantly present in citrus fruits,exhibits significant intervention effects on both the initiation and progression of gastric cancer.However,the specific mechanisms underlying this effect remain unclear.AIM To investigate the interventional role of hesperetin on N-methyl-N’-nitro-Nnitrosoguanidine(MNNG)-induced exosomes in inducing gastric carcinogenesis.METHODS Bioinformatics technology was used to identify the critical molecular components underlying hesperetin-mediated inhibition of MNNG induced gastric carcinogenesis through exosomal circular RNA.Biological experiments were conducted to validate these findings.RESULTS Exosomes derived from TGES-1 cells(TGES-1-EX)significantly enhanced the proliferation,migration,invasion,epithelial-mesenchymal transition(EMT),and stemness of GES-1 cells.The oncogenic potential of TGES-1-EX was significantly diminished following hesperetin pretreatment.TGES-1-EX with overexpressed or knocked down circ0008274 was extracted and GES-1 cells were treated in combination with hesperetin or alone.Our investigation revealed that hesperetin exerted significant inhibitory effects on MNNG-induced gastric carcinogenesis by exosomal circ0008274.Bioinformatics prediction identified microRNA(miR)-526b-5p as a potential miRNA binding to circ0008274.Functional experiments demonstrated that hesperetin may mediate its intervention in MNNG-induced gastric cancer initiation by targeting miR-526b-5p through exosomal circ0008274.TGES-1-EX circ0008274 promoted the proliferation,EMT,and cancer stem cell-like characteristics in GES-1 cells through miR-526b-5p-mediated regulatory mechanisms.CONCLUSION Hesperetin exerted an interventional effect on the gastric carcinogenesis process,particularly through the modulation of exosomal circ0008274 and its interaction with miR-526b-5p.展开更多
基金supported by grants from Youth Fund of the National Natural Science Foundation of China(82303379)General Program of the National Natural Science Foundation of China(81970552)the Natural Science Foundation of Zhejiang Province(LQ23H160030)。
文摘Background:Tumor recurrence severely impacts the prognosis of hepatocellular carcinoma(HCC)patients undergoing liver transplantation(LT).We aimed to explore novel and robust biomarkers for precise prediction of tumor recurrence and prognosis following LT.Methods:Cancerous tissues of 252 HCC patients who underwent LT across three centers were included in the study.Tissue microarrays and in situ hybridization were utilized to assess the circ0006646 level.Kaplan-Meier method along with the log-rank test was performed to analyze overall survival and recurrence-free survival.To identify prognostic factors,particularly related to tumor recurrence,we conducted univariate and multivariate Cox regression analyses.Nomogram was constructed to predict the risk of tumor recurrence after LT and subsequently the efficacy of the nomogram was validated.Results:Elevated circ0006646 levels in HCC were associated with reduced survival and increased recurrence rates following LT(5-year overall survival:29.2%vs.60.4%,P<0.01;5-year recurrence-free survival:42.3%vs.63.0%,P<0.001).High circ0006646 expression was significantly correlated with higher Child-Pugh grade(P=0.040),larger total tumor diameter(P=0.033),and beyond the Milan criteria(P=0.033).Cox regression analysis unveiled that circ0006646 expression score,preoperative transarterial chemoembolization(TACE),positive HBsAg status,poor tumor differentiation and beyond the Hangzhou criteria were independent risk factors for post-transplant tumor recurrence,leading to the development of a novel nomogram for precise prediction.The nomogram demonstrated a reasonable prognostic effectiveness(area under the receiver operating characteristic curve=0.7636,C-index=0.745)and outperformed conventional models like the Milan criteria.Besides,the inclusion of circ0006646 enhanced the precision of the Milan and Hangzhou criteria.Moreover,circ0006646 served as a potent biomarker in alpha-fetoprotein(AFP)-negative HCC undergoing LT.Conclusions:circ0006646 is a novel and robust prognostic biomarker for predicting post-transplant survival and tumor recurrence in HCC patients.A nomogram integrating circ0006646 stands as a valuable prognostic instrument in LT for HCC.
基金Supported by the National Natural Science Foundation of China,No.81602883Technology Development Project of Jiangsu University,No.20220516Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX233765.
文摘BACKGROUND Hesperetin,a flavonoid predominantly present in citrus fruits,exhibits significant intervention effects on both the initiation and progression of gastric cancer.However,the specific mechanisms underlying this effect remain unclear.AIM To investigate the interventional role of hesperetin on N-methyl-N’-nitro-Nnitrosoguanidine(MNNG)-induced exosomes in inducing gastric carcinogenesis.METHODS Bioinformatics technology was used to identify the critical molecular components underlying hesperetin-mediated inhibition of MNNG induced gastric carcinogenesis through exosomal circular RNA.Biological experiments were conducted to validate these findings.RESULTS Exosomes derived from TGES-1 cells(TGES-1-EX)significantly enhanced the proliferation,migration,invasion,epithelial-mesenchymal transition(EMT),and stemness of GES-1 cells.The oncogenic potential of TGES-1-EX was significantly diminished following hesperetin pretreatment.TGES-1-EX with overexpressed or knocked down circ0008274 was extracted and GES-1 cells were treated in combination with hesperetin or alone.Our investigation revealed that hesperetin exerted significant inhibitory effects on MNNG-induced gastric carcinogenesis by exosomal circ0008274.Bioinformatics prediction identified microRNA(miR)-526b-5p as a potential miRNA binding to circ0008274.Functional experiments demonstrated that hesperetin may mediate its intervention in MNNG-induced gastric cancer initiation by targeting miR-526b-5p through exosomal circ0008274.TGES-1-EX circ0008274 promoted the proliferation,EMT,and cancer stem cell-like characteristics in GES-1 cells through miR-526b-5p-mediated regulatory mechanisms.CONCLUSION Hesperetin exerted an interventional effect on the gastric carcinogenesis process,particularly through the modulation of exosomal circ0008274 and its interaction with miR-526b-5p.
